Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cells

By Y. Inami, S. Waguri, A. Sakamoto, T. Kouno, K. Nakada, O. Hino, Sumio Watanabe, J. Ando, Manabu Iwadate, Masayuki Yamamoto and 3 more. Journal of Cell Biology, 2011

599 citations recorded by the source corpus.

Impaired autophagy stabilizes p62 and promotes tumorigenesis through activation of the Nrf2 transcription factor.

Subfields: Epidemiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/88e25bf517da9c80ada3ffeec2cbf6020e32b4ed

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Citations in the corpus

Autophagy: Renovation of Cells and Tissues (2011, background): “, the Atg5 gene is deleted in only some populations of cells in various tissues) or with Atg7 specifically disrupted in hepatocytes (Inami et al., 2011; Takamura et al., 2011).”
Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy. (2013, background): “Although our previous analysis showed that deletion of p62 in JHH5 causes a growth defect in vitro (Inami et al., 2011), the cells may possess somatic mutation(s) of Nrf2 and/or Keap1, similar to the cases of certain cancer cell lines (Kensler et al., 2007; Sporn and Liby, 2012).”
Autophagy in malignant transformation and cancer progression (2015, unknown): “…feedforward loop, stemming from the autophagy-dependent degradation of kelch-like ECH-associated protein 1 (KEAP1, the major negative regulator of NRF2) (Taguchi et al , 2012; Bae et al , 2013), as well as from the NRF2-activating phosphorylation of p62 (Inami et al , 2011; Ichimura et al , 2013).”
The LIR motif – crucial for selective autophagy (2013, background): “Recently, it has been found that the liver toxicity of accumulated p62 is due to constitutive upregulation of the NRF2 oxidative-stressresponse pathway (Inami et al., 2011).”
Oxidative stress response and Nrf2 signaling in aging. (2015, unknown): “autophagy deficiency/p62 accumulation dependent pathway is important in maintaining the integrity of Nrf2-Keap1 system [322-324].”
The dynamic nature of autophagy in cancer. (2011, background): “The Komatsu laboratory (Inami et al. 2011) had similar results with conditional deletion of Atg7 in the liver.”
Autophagy and Tumor Metabolism (2017, result): “Similar results were obtained when Atg7 deletion was targeted to the liver (Inami et al., 2011).”
p62 links autophagy and Nrf2 signaling. (2015, methodology): “Somatic mutations in Nrf2 or its negative regulators (Keap1 and Cul3) have been shown to be responsible for the high levels of Nrf2 in certain tumors, such as lung cancer, melanoma, renal clear cell carcinoma, and hepatocellular carcinoma [53–57].”
Nrf2, the Master Regulator of Anti-Oxidative Responses (2017, background): “[109] also reported that persistent Nrf2 activation, due to the accumulation of p62/SQSTM1, is involved in hepatoma development in Atg7-deficient mice.”